Good Calories, Bad Calories (78 page)

This is yet another example of how the specialization of modern research can work against scientific progress. In this case, endocrinologists studying the role of hormones in obesity, and physiological psychologists studying eating behavior, worked with the same animal models and did similar experiments, yet they published in different journals, attended different conferences, and thus had little awareness of each other’s work and results.

Perhaps more important, neither discipline had any influence on the community of physicians, nutritionists, and psychologists concerned with the medical problem of human obesity. When physiological psychologists published articles that were relevant to the clinical treatment of obesity, they would elicit so little attention, said UCLA’s Donald Novin, whose research suggested that the insulin response to carbohydrates was a driving force in both hunger and obesity, that it seemed as though they had simply tossed the articles into a “black hole.”

The discipline of physiological psychology was founded on Claude Bernard’s notion of the stability of the internal environment and Walter Cannon’s homeostasis. Its most famous practitioner was the Russian Ivan Pavlov, whose career began in the late nineteenth century. The underlying assumption of this research is that behavior is a fundamental mechanism through which we maintain homeostasis, and in some cases—energy balance in particular—it is the primary mechanism. From the mid-1920s through the 1940s, the central figure in the field was Curt Richter of Johns Hopkins. “In human beings and animals, the effort to maintain a constant internal environment or homeostasis constitutes one of the most universal and powerful of al behavior urges or drives,” Richter wrote.

Throughout the first half of the twentieth century, a series of experimental observations, many of them from Richter’s laboratory, raised questions about what is meant by the concepts of hunger, thirst, and palatability, and how they might reflect metabolic and physiological needs. For example, rats whose adrenal glands are removed cannot retain salt, and wil die within two weeks on their usual diet, from the consequences of salt depletion. If given a supply of salt in their cages, however, or given the choice of drinking salt water or pure water, they wil choose either to eat or to drink the salt and, by doing so, keep themselves alive indefinitely. These rats wil develop a “taste” for salt that did not exist prior to the removal of their adrenal glands. Rats that have had their parathyroid glands*132 removed wil die within days of tetany, a disorder of calcium deficiency. If given the opportunity, however, they wil drink a solution of calcium lactate rather than water—not the case with healthy rats—and wil stay alive because of that choice. They wil appear to like the calcium lactate more than water. And rats rendered diabetic voluntarily choose diets devoid of carbohydrates, consuming only protein and fat. “As a result,” Richter said, “they lost their symptoms of diabetes, i.e., their blood sugar fel to its normal level, they gained weight, ate less food and drank only normal amounts of water.”

The question most relevant to weight regulation concerns the quantity of food consumed. Is it determined by some minimal caloric requirement, by how the food tastes, or by some other physical factor—like stomach capacity, as is stil commonly believed? This was the question addressed in the 1940s by Richter and Edward Adolph of the University of Rochester, when they did the experiments we discussed earlier (see Chapter 18), feeding rats chow that had been diluted with water or clay, or infusing nutrients directly into their stomachs. Their conclusion was that eating behavior is fundamental y driven by calories and the energy requirements of the animal. “Rats wil make every effort to maintain their daily caloric intake at a fixed level,” Richter wrote.

Adolph’s statement of this conclusion stil constitutes one of the single most important observations in a century of research on hunger and weight regulation: “Food acceptance and the urge to eat in rats are found to have relatively little to do with ‘a local condition of the gastro-intestinal canal,’ little to do with the ‘organs of taste,’ and very much to do with quantitative deficiencies of currently metabolized materials”—in other words, the relative presence of usable fuel in the bloodstream.†133

The physiological hypothesis of weight regulation and hunger that then emerged in the mid-1970s evolved directly from the work of the French physiological psychologist Jacques Le Magnen, one of the more remarkable figures in the past century of science. Le Magnen was blind, the result of an attack of encephalitis when he was thirteen years old. He compensated by developing what his col eagues described as a “phenomenal” and

“encyclopedic” memory, particularly for the nuances of relevant scientific research. “Jacques Le Magnen knew everything,” as his obituary in the journal Chemical Senses commented after his death in 2002. He was also “incredibly bril iant,” says the University of Cincinnati physiological psychologist Stephen Woods, which seems to be a consensus opinion among those who knew his work. Le Magnen joined the prestigious Col ège de France in 1944, and he remained there for forty years, much of it spent working in the office and laboratory that had original y belonged to Claude Bernard. His Laboratory of Sensory and Behavioral Neurophysiology would eventual y grow to become perhaps the largest in the world focused on issues related to hunger and weight regulation.

Le Magnen’s research on eating behavior began in the early 1950s, when he designed a device to monitor food intake in rats over entire twenty-four-hour cycles. This led him to report that rats ate discrete meals separated in time by discrete intervals. He then set out to establish what factors regulated the size of the meals and the length of the intervals between meals.

Le Magnen’s research resulted in two fundamental observations, both confirming Adolph’s observation that eating behavior in animals, and thus hunger, is driven by those “quantitative deficiencies of currently metabolized materials.”

Le Magnen learned that when rats are al owed to eat whenever they want, the size of the meal determines how long rats wil go before they get hungry again. As a new supply of ingested calories is exhausted by the rat’s energy expenditure, the animal is motivated to eat again. “Al increase or decrease in the two sides of this balance (calories eaten in meals versus metabolic expenditures) wil lead to an immediate shortening or lengthening of the meal-to-meal interval,” Le Magnen explained. And this is “the major and direct agent of the regulation of food intake.”

The second observation was one that is obviously true for humans as wel : Rats eat to excess during their waking hours, which means their intake exceeds their expenditure of energy, and so they are hyperphagic while awake, storing fat during this period. While they’re sleeping, the rats are in negative energy balance—hypophagic—and they live off the fat accumulated during the waking hours. Weight peaks as the rats are going to sleep and it ebbs as they awake. In humans, this cycle would explain, among other things, why hunger doesn’t (or at least shouldn’t) wake us from the depths of a night’s sleep so we can raid the refrigerator.

While rats are sleeping, they progressively mobilize more and more fatty acids from their adipose tissue and use these fatty acids for fuel. “The restitution of these stored fats and their utilization to cover an important part of the current metabolism reduces the concomitant requirement for an external supply of calories by food intake,” Le Magnen wrote. When he used insulin to suppress this mobilization of free fatty acids, the rats ate immediately. Fatty acids released from the adipose tissue, Le Magnen concluded, simply replace or “spare” the available glucose and, by doing so, delay the onset of hunger and the impetus to feed. The liberal availability of these fatty acids in the blood promotes satiety and inhibits hunger.

Another way to phrase this is that anything that induces fatty acids to escape from the fat tissue and then be burned as fuel wil promote satiety by providing fuel to the tissues. Anything that induces lipogenesis, or fat synthesis and storage, wil promote hunger by removing the available fuel from the circulation. And so hypophagia and hyperphagia, satiety and hunger, Le Magnen wrote, are “indirect and passive consequences” of “the neuroendocrine pattern of fat mobilization or synthesis.”

By the mid-1970s, Le Magnen had demonstrated that insulin is the driver of this diurnal cycle of hunger, satiety, and energy balance. At the beginning of waking hours, the insulin response to glucose—the “insulin secretory responsiveness,” Le Magnen cal ed it—is enhanced, and it’s suppressed during sleep. This pattern is “primarily responsible” for the fat accumulation during the waking hours and the fat mobilization during the sleeping hours. “The hyperinsulin secretion in response to food” during the period when the animals are awake and eating, and the “opposite train” when they are asleep, he explained, produces “a successive fal and elevation” of the level of fatty acids in the blood on a twenty-four-hour cycle—twelve hours during which the fatty acids are depressed and glucose is the primary fuel, and then twelve hours in which they’re elevated and fat is the primary fuel. Both hunger, or the urge to eat, and satiety, or the inhibition of eating, are compensatory responses to these insulin-driven cycles of fat storage fol owed by fat mobilization. Insulin secretion is released in the morning upon waking and drives us to eat, Le Magnen concluded, and it ebbs after the last meal of the day to al ow for prolonged sleep without hunger.

This hypothesis of eating behavior did away with set points and lipostats and relied instead on the physiological notion of hunger as a response to the availability of internal fuels and to the hormonal mechanisms of fuel partitioning. Hunger and satiety are manifestations of metabolic needs and physiological conditions at the cel ular level, and so they’re driven by the body, no matter how much we like to think it’s our brains that are in control.

Several variations on this hypothesis were published from the mid-1970s onward by Le Magnen and others. The most comprehensive account was published in 1976 by Edward Stricker at the University of Pittsburgh, and Mark Friedman, then at the University of Massachusetts and now at the Monel Chemical Senses Center in Philadelphia. Their article, “The Physiological Psychology of Hunger: A Physiological Perspective,” should be required reading for anyone seriously interested in eating behavior and weight regulation.

The hypothesis is based on three fundamental propositions. The first, as Friedman and Stricker explained, is that the supply of fuel to al body tissues must always remain “adequate for them to function during al physiological conditions and even during prolonged food deprivation.” The second proposition is Hans Krebs’s revelation from the 1940s that each of the various metabolic fuels—protein, fats, and carbohydrates—is equal y capable of supplying energy to meet the demands of the body. The third is that the body has no way of tel ing the difference between fuels from internal sources—the fat tissue, liver glycogen, muscle protein—and fuels that come from external sources—i.e., whatever we eat that day.

With these propositions in mind, the simplest possible explanation for feeding behavior is that we eat to maintain this flow of energy to cel s—to maintain “caloric homeostasis”—rather than maintain body fat stores or some preferred weight. If the cel s themselves are receiving sufficient fuel to function, the size of the fat reserves is a secondary concern. As Friedman and Stricker explained, “Hunger appears and disappears according to normal y occurring fluctuations in the availability of utilizable metabolic fuels, regardless of which fuels they are and how ful the storage reserves.” In 1993, the Princeton physiological psychologist Bartley Hoebel described the hypothesis in terms that echoed the origins of the theory in the work of Claude Bernard: “The primitive goal of feeding behavior,” Hoebel explained, “is to maintain constancy of the nutrient concentration of the milieu intérieur.”

From this perspective, we’re not much more complicated than insects, which wil seek out food and consume it until their guts are ful . External taste receptors signal whether they’ve come upon something they can benefit from eating; gut receptors signal when sufficient food has been consumed to inhibit the hunger. The role of the brain is to integrate the sensory signals from the gut and the taste receptors and couple them to motor reflexes to initiate eating behavior or inhibit it. In both flies and mosquitoes, if the neural connection between gut and brain is severed, the insect loses its hunger inhibitor and continues to eat until its gut literal y ruptures. As Edward Stricker explained in The New England Journal of Medicine in 1978, hunger is little more than a disturbing stimulus, like an itch, that “feeding behavior removes or attenuates.” Satiety, on the other hand, “is more than the absence of hunger; it is the active suppression of interest in food and of feeding behavior.”

The primary difference between humans and insects, by this logic, is that we have two primary fuel tanks (three if we include glycogen stored in the liver, and four if we include protein in the muscles), and they effectively have one. In our case, fuel is stored initial y in the gut for the short term, and then in the fat tissue for the medium to longer term. The fat tissue extends the time we can go between meals by hours, days, or more. The fuel supply to the cel s is maintained by the fil ing and emptying of both these energy reserves. “Energy metabolism,” Friedman and Stricker wrote, “is maintained by alternating tides of nutrients that sweep in from the intestines or adipose tissue at regular intervals depending on when food consumption occurs.” The fat tissue participates actively in metabolism by acting as an energy buffer: it provides storage for nutrients that arrive with the meal but are not immediately necessary for energy, and then it releases them back into the circulation as this absorptive phase is coming to an end. In effect, the fat tissue prevents dramatic shifts in the energy supply, which would otherwise be unavoidable considering the fact that, unlike cattle or sheep, we don’t graze continual y but, rather, eat episodical y in discrete meals.